2,6-Dimethylphenol → Methyl 6-[4-({[3-{[(2,6-dimethylphenyl)oxy]methyl}-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate

HRID 2423460Notes

Reaction equation

HRID 2423460 reaction equation
[OH:1][CH2:2][C:3]1[C:7]([CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:17]=[C:18]4[C:23](=[CH:24][CH:25]=3)[N:22]=[C:21]([C:26]([O:28][CH3:29])=[O:27])[CH:20]=[CH:19]4)=[CH:12][CH:11]=2)=[C:6]([CH:30]([CH3:32])[CH3:31])[O:5][N:4]=1.[CH3:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([CH3:40])[C:35]=1O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>ClCCl>[CH3:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([CH3:40])[C:35]=1[O:1][CH2:2][C:3]1[C:7]([CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:17]=[C:18]4[C:23](=[CH:24][CH:25]=3)[N:22]=[C:21]([C:26]([O:28][CH3:29])=[O:27])[CH:20]=[CH:19]4)=[CH:12][CH:11]=2)=[C:6]([CH:30]([CH3:32])[CH3:31])[O:5][N:4]=1

Participants

6

Reactant 4

HCID 113352,6-DimethylphenolHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 59321462Methyl 6-[4-({[3-(hydroxymethyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate

Product 1

HCID 59321594Methyl 6-[4-({[3-{[(2,6-dimethylphenyl)oxy]methyl}-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylateYield 31%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of methyl 6-[4-({[3-(hydroxymethyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate (60 mg, 0.14 mmol), 2,6-dimethylphenol (17 mg, 0.14 mmol) and triphenylphosphine (40 mg, 0.15 mmol) in dichloromethane (1.5 mL) was added diisopropyl azodicarboxylate (0.028 mL, 0.15 mmol) dropwise. The solution was stirred at ambient temperature for approximately 1.5 hours and then in a microwave reactor at 100° C. for 10 minutes. The solution was adsorbed onto silica gel and purified by chromatography (silica gel, 0-40% ethyl acetate gradient elution). The resulting residue was taken up with ether and sonicated until a solid precipitated. The solid was isolated by filtration to afford methyl 6-[4-({[3-{[(2,6-dimethylphenyl)oxy]methyl}-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate (23 mg, 31%). 1H-NMR (400 MHz, CDCl3) δ 8.37-8.32 (m, 2H), 8.23-8.21 (m, 1H), 8.05-8.01 (m, 2H), 7.69 (d, J=9 Hz, 2H), 7.08 (d, J=9 Hz, 2H), 7.01-6.01 (m, 3H), 5.04 (s, 2H), 4.96 (s, 2H), 4.09 (s, 3H), 3.29 (septet, J=7 Hz, 1H), 2.23 (s, 6H), 1.38 (d, J=7 Hz, 6H).

Workup

  1. waitin a microwave reactor at 100° C. for 10 minutes
  2. custompurified by chromatography (silica gel, 0-40% ethyl acetate gradient elution)
  3. customsonicated until a solid
  4. customprecipitated
  5. customThe solid was isolated by filtration

Sources & evidence

ORD record
ord-92efb30207d54a8b98c4fe3fb96dde92
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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